Synthesis of unprotected thienyl sulfonamides and their activities against carbapenem-resistant Klebsiella pneumoniae, docking studies and ADMET analysis

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP), in particular hypervirulent and classical strains, represents a severe global health burden with limited treatment options. The urgent need for new antimicrobials motivates the exploration of novel chemical scaffolds. This study focused on substituted thiophene-based thienyl sulfonamides, synthesized via the Suzuki–Miyaura cross-coupling with moderate to excellent yields of unprotected compounds. Evaluation against clinical CRKP isolates revealed significant antibacterial activity for several synthesized sulfonamides. Molecular docking and ADMET profiling further identified compounds 3c, 3f, and 3g as possessing potent activity, promising binding characteristics, and suitable pharmacological properties. These results highlight these thienyl sulfonamides as viable lead candidates for combating multidrug-resistant K. pneumoniae infections.